Vertical transmission of human immunodeficiency virus (HIV) from mother to child is a major problem in sub-Saharan Africa. As in adults, a variety of cognitive impairments may be evident in HIV infected children being treated with combined antiretroviral therapy (ART). The HIV virus compromises visual perception, attention, memory, language and executive functioning. Prior imaging studies have shown abnormal brain structure in adults and children infected by HIV. Graph theory analyses have been applied to HIV neuropathogenesis previously, these have demonstrated significant disruptions to brain connectivity in older HIV+ adults on treatment. However, no previous studies have investigated the same topological organization or structural connectivity of brain structure in infected children, or correlated this with markers of disease severity. The aims of this project were first, to delineate the topological organization of brain structure in children living with HIV currently on treatment and contrast it with healthy HIV negative children, second to investigate differences in measures of brain structure between healthy controls and children living with HIV and third to correlate brain imaging measures with markers of disease severity. The studies presented here examine the structural connectivity between nodes in the brain by utilizing magnetic resonance imaging and graph theory methods, and also investigated gray matter structure and cortical complexity. Children living with HIV displayed abnormal structural connectivity in regions of the dorsal posterior cingulate and inferior frontal gyrus of the frontal lobe, as well as in superior regions of the temporal lobe when compared to healthy HIV negative children. Significantly decreased cortical thickness was found in precentral and postcentral regions and the superior and middle frontal regions of children living with HIV compared to the healthy group. Deficits in cortical complexity of the inferior frontal gyrus and fusiform gyri were also apparent in the HIV infected group. Cortical thickness, surface area and gyrification were positively associated with CD4 count as a marker of disease severity. In conclusion, this project demonstrated abnormal brain structure and structural connectivity of brain structure in regions involved with motor development, executive function, and language fluency and generation in treated children living with HIV. Abnormal structural connectivity may indicate disruption to brain network integrity in developing children. Even in the post-ART era, infected children remain at risk for abnormal brain development. Longitudinal studies in larger cohorts are needed to address the issue of changes in brain structure and topology over time during adolescent brain development.

International migration has reached an all-time high in 2015 where many global states were not able to keep up with the numbers of people crossing political borders. With many reasons to flee a landscape, both refugees and undocumented immigrants face the continued stressors that are part of the migratory journey, even years after their journey is over. Many who fled during this time frame were escaping war in Syria, while many others were escaping economic devastation, gender violence, and other forms of insecurity all over the world. Evidence has shown that groups who have experienced violent geographies who have been forcibly displaced have higher rates of psychiatric illness than those who were not exposed to these stressful conditions. The effects of toxic stress do not stop once the individual is taken out of the traumatic landscape; it stays within the individual as they continue their life. This study will discuss additional stressors associated with the migratory experience during and after resettlement. This thesis discusses three groups of actors associated with migration including NGOs, migrating people, and citizens affected by migration. It will discuss personal accounts of refugees and NGOs who have experience with displacement. This thesis will focus particularly on issues such as mental health and access to health, education, and employment services for displaced populations. This thesis will also discuss indicators of psychiatric illness in displaced populations and present-day solutions to restructure contemporary immigration systems around the world.

Depression in the perinatal period carries a significant burden of disease and can have negative impacts on foetuses and infants of mothers suffering from the illness. Risk factors for perinatal depression are particularly high in Low- and Middle-Income Countries (LMICs), and include partner abuse, economic insecurity, HIV, unwanted pregnancy, and food insecurity. Despite the substantial burden, there is a considerable 'treatment gap' between the need for treatment and the provision of services for perinatal depression in LMICs. Task sharing using non-specialist health workers has been recommended as a costeffective means to address this treatment gap and reduce the burden on mental health specialists in public health services. Evidence has shown moderate effects of task-shared treatments on the reduction of perinatal depression, but little is known about the processes, mechanisms and elements that lead these treatments to be effective. This thesis is nested within the Africa Focus on Intervention Research for Mental Health - South Africa (AFFIRM-SA) randomised controlled trial (RCT), which aimed to test a task-shared psychological treatment for perinatal depression in Khayelitsha, a low-income township outside of Cape Town in South Africa. The aim of this thesis was to explore the mechanisms of implementation and change of this intervention through a process evaluation. Before implementation of the intervention, qualitative research was employed to explore the idioms, symptoms and perceived causes of depression particular to perinatal women living in Khayelitsha, using semistructured interviews and a framework analysis approach. This was conducted with 12 depressed and nine non-depressed pregnant women and mothers of young babies, and 13 health care providers. These idioms and symptoms were also compared with the ICD 10 and DSM-5 criteria for major depression. The research found that local idioms used to describe depression included 'stress', 'thinking too much', being sad or unhappy, and being scared. Some of the common symptoms of depression were expressed as withdrawal and not wanting to talk, crying or sadness, poor concentration, thinking too much, fear and anxiety, stress, sleep problems, headaches, and body pain. The primary causes that women attributed to these depressive symptoms were lack of support, having an unwanted pregnancy, death of a loved one, poverty, unemployment, thinking too much, coping with a new baby, and stress. These were exacerbated by the extreme risk factors the women faced in Khayelitsha such as low income levels, poverty, partner abuse, low education levels, poor housing and living conditions, and poor health care. The findings from this research were recommended for inclusion in the development of the counselling intervention manual for the RCT. Following implementation of the AFFIRM-SA RCT counselling intervention, the trial outcome assessments found non-significant effects in the reduction of depressive symptoms on the Hamilton Depression Rating scale (HDRS) at three and 12 months post-partum, but also found significant improvements on the Edinburgh Postnatal Depression Scale (EPDS) at both time points for the intervention group, compared to the control group. The process evaluation for this thesis subsequently examined mechanisms and contextual factors that may have influenced the intervention outcome. This involved reviewing the counselling manual and conducting a grounded theory analysis of a sample of the counselling session transcripts from the intervention. The review of the counselling manual found that the structure, layout, instructions and grammar in the manual may have led to some difficulties in its interpretation and use for counsellors and participants. The grounded theory analysis included 39 participants who had completed all six sessions of the intervention (totalling 234 sessions). The use of grounded theory allowed for findings to emerge which had not been prespecified before analysis. This process began with the identification of 'open codes', which was anything that 'stood out' from the data. Following this, a secondary 'axial coding' of the data then identified four themes that encompassed all of the open codes. The themes were: therapeutic breakdowns in the counselling sessions, the adverse influence of socio-economic context on therapeutic effectiveness, reported positive outcomes, and attributes given for the reported changes. In turn, these themes could be represented by one of two 'core concepts' that characterised the processes that occurred during the counselling sessions. These were deviations from the intended counselling protocol (when things fall apart), and effectiveness of the counselling sessions (when things come together). The third level of coding, termed 'selective coding', examined the potential reasons for the deviations from protocol and the mechanisms or elements behind the attributions of the reported outcomes. Possible reasons for deviations include the original context of the development of the intervention, not fully incorporating the formative research and pilot findings, the limited skill base of the counsellors, limited training and supervision, the structure and design of the intervention, ownership by the counsellors of the intervention, the role of advice in this context, and contextually related need from the participants. This also explained potential reasons for the non-significant effects of the intervention on the HDRS. In terms of the attributions that the participants gave for their outcomes of change, many of these acted as 'mechanisms' or therapeutic elements of the counselling, and these elements were similar to previous research on common or 'non-specific' elements in the therapeutic space. These elements played an important role in participants' feelings of connection and reduction of distress, despite evidence of deviations from the counselling protocol. This was in keeping with the significant effects of the intervention on the EPDS outcomes. The thesis presents two models of processes that occurred in the intervention. The first posits that the intervention did not sufficiently disrupt the mechanisms or context that creates and perpetuates depression to enable long term shifts or significant changes in clinical depressive symptoms. The second suggests that the intervention provided a sense of connection and a subsequent 'buffer' of resilience to handle every-day stressors, but that this buffer was short-term and could not provide longer-term resilience against the extreme context of poverty, unemployment, abuse and trauma. Through a process evaluation of the design and implementation of the AFFIRM-SA intervention, this thesis presents a wide range of contextual considerations and therapeutic elements relevant to designing and implementing more acceptable and responsive public mental health interventions that aim to bring about real and sustainable change for perinatal depression in South Africa and other LMICs.

This study used a longitudinal design to investigate the relation between depression and pessimism-related cognitions about the self, world, and future in a clinical sample of psychiatric inpatients. A group of 30 inpatients diagnosed with major depressive illness was compared with a mixed-diagnostic comparison group of 28 inpatients on a measure of syndromal depression, as well as on pessimism-related cognitive measures of self-esteem, perceptions of the benevolence of the world, and hopelessness. All subjects completed the measures at two time points: within four days of admission to an psychiatric inpatient unit, and an average of 13.5 days later. It was expected that the nosologically depressed group would endorse more negative pessimism-related cognitions than the comparison group, that the pessimism-related cognitions would persist beyond remission of depressive symptoms, and that Time 1 cognitions would significantly predict Time 2 depression after controlling for depression at Time 1. Contrary to expectations, groups did not differ on the measure of syndromal depression, nor on the measures of cognitions pertaining to the self and future. Both groups exhibited a significant decline in depressive symptoms over time. Moreover, scores on the pessimism-related cognitive measures changed in concert with scores on the depression measure, and did not predict Time 2 depression. Additionally, significant interactions of group, gender, and time on the measure of syndromal depression, and interactions of group and gender on the cognitive measures, were found. These interactions revealed that men in the nosologically depressed group scored significantly lower than men in the comparison group on the measure of syndromal depression, and endorsed more positive cognitions about the self, world, and future. These findings refute major theoretical postulates regarding depressotypic cognitions, in that pessimism-related cognitions were: (1) not specific to nosological depression; (2) were mood-state dependent, with the exception of cognitions about the world; and (3) did not serve a maintenance function in syndromal depression. Exploratory analyses suggest that for the depressed group only, hopelessness may significantly predict Time 2 depression, and thus serve to prolong depression. The theoretical and clinical implications of all findings are discussed.

Introduction. Numerous studies, conducted in many different countries, report that cognitive impairment is highly prevalent in people with HIV (PWH). Such impairment can affect adherence to antiretroviral therapy (ART), and adherence is, in turn, essential for PWH to achieve viral suppression. The gold standard to confirm cognitive impairment is a neuropsychological assessment. However, accurate interpretation of neuropsychological test performance requires consideration of, for instance, how impairment is determined and how accurately the contribution of non-HIV factors to poor cognitive test performance is described. These non-HIV factors include sociodemographic variables (e.g., age, sex, educational attainment), psychosocial variables (e.g., socioeconomic status, food security, quality of life), psychiatric variables (e.g., depression, problematic alcohol use), and other medical co-morbidities. Because many existing studies of PWH do not account for (a) the fact that current quantitative methods for defining cognitive impairment may not accurately reflect HIV-associated brain injury, and (b) possible contributions of non-HIV factors to cognitive test performance, it is possible that the reported prevalence rates of cognitive impairment in PWH are inaccurate (or, at least, do not solely reflect the contributions of HIV disease to the impairment). Another uncertainty in the HIV neuropsychology literature concerns sex differences in the cognitive performance of PWH. Some recent studies suggest that women with HIV (WWH) may present with greater cognitive impairment than men with HIV (MWH). Such a sex difference is of potentially significant concern for South African clinicians because two-thirds of the population of PWH in this country are women. However, there is no definitive empirical evidence regarding whether this sex difference exists to a clinically significant degree (in South Africa, specifically, as well as globally) and what its underlying mechanisms might be. To address the knowledge gaps outlined above, this thesis set out to explore the following aims: (1) investigate sex differences in the cognitive performance of PWH by reviewing the current published literature; (2) determine if sex differences exist in a clinic sample of South African PWH; (3) determine how much variation in reported prevalence rates of HIV-associated cognitive impairment are due to the method used to define impairment, and which method correlates best with MRI biomarkers of HIVrelated brain injury in a South African sample of PWH; (4) investigate the contribution of sociodemographic and psychosocial variables, as well as HIV-disease factors and other medical and psychiatric comorbidities, to cognitive performance in a South African sample of PWH; and (5) investigate associations between cognitive performance and ART adherence in 10 a South African sample of PWH. Each of these aims was explored in a separate study. Hence, this thesis reports on findings from five separate journal manuscripts. Method. Study 1 was a systematic review and meta-analysis summarizing the findings of published studies investigating differences in cognitive performance between WWH and MWH. An extensive systematic search of the literature across several databases found 4062 unique articles of potential interest. After thorough screening of that pool of articles, 11 studies (total N = 3333) were included in the narrative systematic review and 6 studies (total N = 2852) were included in the meta-analysis. Effect sizes were calculated to estimate between-sex differences in cognitive performance, both globally and within discrete cognitive domains. Study 2 investigated sex differences in cognitive performance in a sample of PWH with comorbid MDD (N = 105). All participants were attending community clinics in Khayelitsha, a peri-urban community in Cape Town, South Africa, and were part of a larger research program for a randomised controlled trial of a cognitive-behavioral treatment for ART adherence and depression (CBT-AD). As part of this program, they completed baseline neuropsychological, psychiatric, and sociodemographic assessments. T-tests and multivariable regressions controlling for covariates compared baseline cognitive performance of WWH and MWH, both globally and within discrete cognitive domains. Study 3 applied 20 different quantitative methods of determining cognitive impairment to existing data from a different sample of PWH (N = 148). These individuals had also been recruited from community clinics in Khayelitsha, and had completed a comprehensive neuropsychological assessment and a 3T structural MRI and diffusion tensor imaging (DTI) session. Logistic regression models investigated the association between each method and HIV-related neuroimaging abnormalities. Study 4 again used data from the sample of PWH with comorbid MDD who participated in the larger CBT-AD research program. This study investigated which sociodemographic, psychosocial, psychiatric, and medical variables (as measured at baseline) were associated with baseline cognitive performance. Post-baseline, 33 participants were assigned to CBT-AD and 72 to standard-of-care treatment; 81 participants (nCBT-AD = 29) had a follow-up assessment 8 months post-baseline. This study also investigated whether, from baseline to follow-up, depression and cognitive performance improved significantly more in the participants who had received CBT-AD, and examined associations between post-intervention improvements in depression and cognitive performance. Study 5 assessed ART adherence in the same sample of PWH with comorbid MDD. Mixed-effects regression models estimated the relationship between ART adherence (as measured by both self-report and objective measures, and by degree of HIV viral suppression) with cognitive performance 11 and with other sociodemographic, psychosocial, and psychiatric variables at both baseline and follow-up. Results. Study 1: Analyses suggested that, in terms of overall cognitive functioning, there were no significant differences in cognitive performance between WWH and MWH. However, WWH did perform significantly more poorly than MWH in the domains of psychomotor coordination and visuospatial learning and memory. Additionally, the review suggested that cognitive differences between WWH and MWH might be accounted for by sex-based variation in educational and psychiatric characteristics among study samples. Study 2: Analyses suggested that, in our sample of PWH with comorbid MDD, there were no significant differences in cognitive performance between WWH and MWH. Study 3: Findings suggested that there was marked variation in rates of cognitive impairment (20– 97%) depending on which method was used to define impairment, and that none of these methods accurately reflected HIV-associated brain injury. Study 4: Analyses suggested that less education and greater food insecurity were the strongest predictors of global cognitive performance. Improvement in depression severity was not significantly associated with improved cognitive performance, except in the domain of Attention/Working Memory. Overall, factors associated with cognitive performance were unrelated to HIV disease and other medical factors. Study 5: Analyses identified poor global cognitive performance as a potential barrier to achieving HIV suppression. Conclusion. Taken together, the findings from the five studies contained within this thesis suggest that one oft-mooted sociodemographic influence on cognitive performance in PWH, sex, was not a consistent influence on such performance. However, non-biological (mainly psychosocial and socioeconomic) factors were stronger predictors of cognitive performance in PWH than medical factors (including HIV-disease variables). Current quantitative criteria for defining cognitive impairment in PWH also do not accurately reflect the biological effects of HIV in the brain. The implication of these findings is that research studies may be misclassifying PWH as cognitively impaired and consequently overestimating the prevalence of cognitive impairment in this population. When conducting clinical assessments of PWH, future research studies should measure and consider the strong influence of psychosocial and socioeconomic factors on cognitive test performance. Ideally, a diagnosis of impairment should only be made after a comprehensive clinical assessment that includes a detailed history taking. Overall, we need new criteria for defining cognitive impairment in diverse global populations of PWH. Ideally these criteria should be applicable to both research and clinical settings. Assessing for cognitive impairment among PWH and then providing 12 appropriate support could help achieve viral suppression in patients with non-optimal adherence to ART. At public policy levels, addressing larger psychosocial issues (e.g., food insecurity and low educational attainment) may also help improve cognitive performance in PWH.

Introduction: Mental health in the workplace has emerged as an important issue and a number of pieces of legislation at the international and regional level provide a good framework for ensuring that people with mental disorders have equal opportunities for employment and support within the workplace. This issue has not been sufficiently addressed in Namibia. This study therefore explored how mental illness is addressed in human resources policies, processes, procedures, and mental health programmes in the Namibian Public Service workplace. Methods: This study comprised two components: a review of legal documents and a qualitative study with relevant people addressing mental illness in the workplace. Five existing Laws, Policies and Rules were reviewed. The review looked at any reference to Mental Illness or Mental Health and in instances where both were not used, identified other terms used like, severe psychiatric illness, psychological disorders, MNS disorders (mental, neurological and substance abuse). In cases where none of the terms were used to identify the two concepts or general health or illness in all documents, the review identified other terms or phrases that may have been used to identify physical or mental illness. The review further pinpointed the legal provisions in the laws which have direct reference to mental illness in the workplace. These provisions ranged from recruitment, management, and boarding of people with mental illness in the workplace. In the second component, a qualitative study design was used comprising of three semi-structured interviews and seven focus group discussions. The study had a total of thirty nine participants selected through a purposeful sampling method. Two representatives, one from each of the unions representing employees in the public service and one participant from the Medical Review Board were interviewed individually. Sixteen Government Ministries were selected and invited to participate in the study, but only nine sent a total of twelve representatives from HR Departments to participate. The Public Service Commission focus group discussion had twelve participants, while members of the Mental Health Association of Namibia representing people with mental illness (MI) and their support persons participated in two focus groups. Four participants who had experienced being medically boarded due to MI, participated in two focus group discussions. All sessions were audio recorded and transcribed verbatim. A Framework Data Analysis approach was used to extract themes to address the aim and objectives. Results: The findings from the document review show that the legislation framework lacked clear documentation of how to identify and manage mental illness in the workplace, resulting in inconsistencies in how mental illness is managed in the Namibian public sector. The findings of the qualitative study show that participants have limited knowledge of what mental illness is, although people seemed able to describe how to recognize someone with mental illness from the way they act. There is confusion between the concepts of disability and ill-health resulting in many people being boarded prematurely or inappropriately. Conclusion: The participants appreciated and recognized the importance of the study in all the discussions, suggesting that there is a need for platforms to be created where issues of mental illness and mental health can be discussed. The lack of a coordinating structure for mental illness in the Public Service was seen a stumbling block in addressing mental illness in an appropriate way. The recommendations to have at least one trained health worker who will be dedicated to employee wellness, will be a step in the right direction. There is an urgent need to reform some of the legal instruments to be able to create a positive impact for people with mental illness in the workplace.

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